Adherence to subcutaneous interferon beta-1a treatment among patients with relapsing multiple sclerosis: the MAIN-MS study.

Introduction and background: Adherence is a critical factor for optimal clinical outcomes in multiple sclerosis (MS) treatment. This study investigated the adherence and clinical outcomes of MS patients treated with subcutaneous (sc) interferon (IFN) (ß)-1a, an established immunomodulatory treatment for relapsing MS. The benefits of a patient support programme (PSP) were also studied. Methods: This phase-IV prospective, observational multicentre study enrolled patients with relapsing MS who were treated with sc IFN ß-1a for 24 months was conducted at 53 centres across 17 countries. The primary endpoint was adherence to sc IFN ß-1a treatment, as assessed using Morisky Green Levine Medication Adherence Scale (MGLS) scores at 24 months. The MGLS is a self-reported diagnostic tool to address medication non-adherence, with a score ranging from 0 to 4, with 0 representing high adherence, 1-2 representing medium adherence, and 3-4 representing low adherence. Other endpoints included time to study and treatment discontinuation over 24 months, the proportion of relapse-free patients, and Expanded Disability Status Scale (EDSS) progression (defined as ≥1.0 point increase sustained for 3 months) at 24 months. A subgroup analysis was performed for endpoints based on patients assigned to PSP (yes/no-PSP versus non-PSP subgroup). Results: Of the 577 patients enrolled, 408 had evaluable MGLS scores at 24 months. A total of 336 (58.2%; 95% confidence interval [CI]: 54.1-62.3%) patients reported high adherence, 57 (9.9%; 95% CIs: 7.6-12.7%) reported medium adherence, and 15 (2.6%; 95% CI: 1.5-4.3%) reported low adherence at 24 months. The PSP subgroup reported higher adherence (n = 206; 65.8%) than the non-PSP subgroup (n = 130; 56.5%). By 24 months, 52.2% of the patients were relapse-free and 17.2% patients experienced ≥1 relapse. Expanded Disability Status Scale progression was observed in 12.3% of patients. Over the 24-month period, 30.8% of the patients discontinued treatment, and the most common reasons for treatment discontinuation were adverse events (AEs, 10.4%), being lost to followup (7.1%), and a lack of efficacy (5.5%). Overall, 39.6% patients experienced ≥1 AE, which ranged from mild to moderate. Conclusion: The study demonstrated high adherence to sc IFN ß-1a treatment with an added benefit of PSP participation. More than half of the patients remained relapse-free over a 24-month period. No new safety concerns to sc IFN ß-1a treatment were observed. Clinical trial registration: https://clinicaltrials.gov/study/NCT02921035, NCT02921035.

Saudi consensus recommendations on the management of multiple sclerosis: MS management in children and adolescents.

Multiple sclerosis (MS) most commonly presents in young adults, although 3-5% of patients develop MS prior to the age of 18 years. The new and comprehensive consensus for the management of MS in Saudi Arabia includes recommendations for the management of MS and other CNS inflammatory demyelinating disorders in pediatric and adolescent patients. This article summarizes the key recommendations for the diagnosis and management of these disorders in young patients. Pediatric and adult populations with MS differ in their presentation and clinical course. Careful differential diagnosis is important to exclude alternative diagnoses such as acute disseminated encephalomyelitis (ADEM) or neuromyelitis optica spectrum disorders (NMOSD). The diagnosis of MS in a pediatric/adolescent patient is based on the 2017 McDonald diagnostic criteria, as in adults, once the possibility of ADEM or NMOSD has been ruled out. Few data are available from randomized trials to support the use of a specific disease-modifying therapy (DMT) in this population. Interferons and glatiramer acetate are preferred initial choices for DMTs based on observational evidence, with the requirement of a switch to a more effective DMT if breakthrough MS activity occurs.

Saudi consensus recommendations on the management of Neuromyelitis Optica Spectrum Disorders (NMOSD).

This article focuses on the diagnosis and management of neuromyelitis optica spectrum disorder (NMOSD). NMOSD is an autoimmune, demyelinating condition characterized by inflammation of the optic nerve and/or the spinal cord, with symptoms that can range from mild impairment of movement to paralysis. The newly approved diagnostic criteria have improved the accuracy of NMOSD diagnosis. The management of NMOSD is under major revolution due to the many new therapeutic options. The role of the antibodies directed at aquaporin-4 (AQP4) has materialized as a biomarker for NMOSD. Several new treatments that target variable aspects in immunopathology such as IL-6, complement, or depletion of B cells are emerging. The management of AQP4-negative patients remains challenging.

A Multidisciplinary Perspective Addressing the Diagnostic Challenges of Late-Onset Pompe Disease in the Arabian Peninsula Region Developed From an Expert Group Meeting.

Pompe disease is a rare, metabolic, autosomal recessive disorder. Early diagnosis is critical for progressive Pompe disease as delays can significantly alter the clinical course of the disease. Diagnostic modalities, including dried blood spot testing and genetic testing, are available and are effective for diagnosing patients with late-onset Pompe disease (LOPD). However, clinicians face numerous clinical challenges related to the diagnosis of the disease. Two expert group committee meetings, involving 11 experts from the United Arab Emirates, Kuwait, the Kingdom of Saudi Arabia, and Oman, were convened in October 2019 and November 2020 respectively to develop a uniform diagnostic algorithm for the diagnosis of pediatric and adult LOPD in the Arabian Peninsula region. During the first meeting, the specialty-specific clinical presentation of LOPD was defined. During the second meeting, a diagnostic algorithm was developed after a thorough validation of clinical presentation or symptoms, which was performed with the aid of existing literature and expert judgement. A consensus was reached on the diagnostic algorithm for field specialists, such as neurologists, rheumatologists, general practitioners/internal medicine specialists, orthopedic specialists, and pulmonologists. This specialty-specific diagnostic referral algorithm for pediatric and adult LOPD will guide clinicians in the differential diagnosis of LOPD.

The disease course of multiple sclerosis before and during COVID-19 pandemic: A retrospective five-year study.

INTRODUCTION: COVID-19 pandemic is thought to influence the natural history of immune disorders, yet the knowledge on its effect on multiple sclerosis (MS) is unknown and not fully understood for which we conducted this retrospective study. METHODS AND MATERIALS: We included all patients with MS seen in King Faisal Specialist Hospital and Research Centre in Jeddah, Saudi Arabia, between January 2017 and October 20201. We determined clinical and radiological evidence of disease activities in all patients by the end of the study period, and we compared the disease patterns before and during the pandemic. We also identified patients with COVID-19 since March 2020, who had at least 3 months of follow-up following the infection. RESULTS: We studied 301 patients; 216 (72%) were women, the mean age was 38 years (range; 16, 73 years), the mean disease duration was 10 years (range; 1, 36 years), and the median EDSS score was 0.5 (range; 0, 8). RRMS accounted for most of the cases (270 patients). MS disease activities were 25% less prevalent during the pandemic compared to the preceding 3 years (26 vs. 51%, respectively, p < 0.01). Bivariate analysis showed significant higher disease activities in patients younger than 35 years (73 vs 27%), on DMT (68 vs 32%), and complaint to therapy (69 vs 31%). Multiple logistic regression analysis showed that the likelihood of MS disease activities were 3 times more during the pre-pandemic era (adjusted OR = 3.1, p value < 0.05, 95% CI; 1.4, 7.1). Thirty patients (10%) were infected with COVID-19. All patients reported mild symptoms, and none required hospitalization. COVID-19 was prevalent among younger patients with RRMS, with low EDSS scores, irrespective of DMTs they received. COVID-19 infection was not associated with clinical relapses or MRI changes. Disease activities were dependent on DMT use and not COVID-19 status. Multivariate analyses also confirmed no effect of COVID-19 on disease activities (p = 0.3 and 0.4, for clinical and MRI changes, respectively). CONCLUSIONS: MS disease activities did not increase during the pandemic, yet the apparent decrease in the disease activities is probably due to under reporting and not a real decrease in disease activities because of the pandemic. The COVID-19 infection in our MS patients showed a benign disease course, yet standard precautions to reduce the risk of COVID-19 transmission should be applied accordingly.

SARS-COV-2 Triggers the Development of Class I and Class II HLA Antibodies in Recovered Convalescent Plasma Donors.

Various studies have shown that SARS-CoV-2 is a highly immunogenic virus. It is known that different types of immunogenic viral pathogens could trigger the formation of HLA antibodies. Therefore, there is a concern that the SARS-CoV-2 could also induce the development of HLA antibodies in volunteers, who donate convalescent plasma after their recovery from COVID-19. HLA antibodies have been identified as the main cause for transfusion-related acute lung injury (TRALI), a well-documented life-threatening complication of transfusions. The TRALI risk could be high in COVID-19 patients who need convalescent plasma, as such patients usually have already an impaired respiratory system affected by the SARS-CoV-2 infection. In this study, we screened 34 convalescent plasma donors on the presence of antibodies against HLA class I and II antigens. All included donors have no any history of sensitization events such as blood transfusions, pregnancy, or previous transplants. We found a high rate of HLA antibody formation in convalescent plasma donors. The frequency of positivity for HLA antibodies for class I, class II, class I and II, and the overall reactivity was 23%, 31%, 46%, and 76%, respectively. The presented data suggest a closed correlation between SARS-CoV-2 virus infection and the development of HLA antibodies in recovered convalescent plasma donors. This finding might have the potential to reduce the risk of TRALI and mortality rate in COVID-19 patients by implementing HLA diagnostic strategies before the administration of convalescent plasma.

Clinical, Neurophysiological, Radiological, Pathological, and Genetic Features of Dysferlinopathy in Saudi Arabia.

Background: To characterize the phenotypic, neurophysiological, radiological, pathological, and genetic profile of 33 Saudi Arabian families with dysferlinopathy. Methods: A descriptive observational study was done on a cohort of 112 Saudi Arabian families with LGMD. Screening for the Dysferlin (DYSF) gene was done in a tertiary care referral hospital in Saudi Arabia. Clinical, Neurophysiological, Radiological, Pathological, and Genetic findings in subjects with dysferlin mutation were the primary outcome variables. Statistical analysis was done by Epi-info. Results: 33 out of 112 families (29.46%) registered in the LGMD cohort had Dysferlinopathy. 53 subjects (28 males, 52.83%) from 33 families were followed up for various periods ranging from 1 to 28 years. The mean age of onset was 17.79 ± 3.48 years (Range 10 to 25 years). Miyoshi Myopathy phenotype was observed in 50.94% (27 out of 53), LGMDR2 phenotype in 30.19% (16 out of 53), and proximodistal phenotype in 15.09% (8 out of 53) of the subjects. Loss of ambulation was observed in 39.62% (21 out of 53 subjects). Electrophysiological, Radiological, and histopathological changes were compatible with the diagnosis. Mean serum Creatinine Kinase was 6,464.45 ± 4,149.24 with a range from 302 to 21,483 IU/L. In addition, 13 dysferlin mutations were identified two of them were compound heterozygous. One founder mutation was observed c.164_165insA in 19 unrelated families. Conclusion: The prevalence of Dysferlinopathy was 29.46% in the native Saudi LGMD cohort. It is the most prevalent subtype seconded by calpainopathy. The clinical course varied among the study subjects and was consistent with those reported from different ethnic groups. One founder mutation was identified. Initial screening of the founder mutations in new families is highly recommended.

Real-world effectiveness and safety profile of teriflunomide in the management of multiple sclerosis in the Gulf Cooperation Council countries: An expert consensus narrative review.

Background: The prevalence of multiple sclerosis (MS) is increasing in Gulf Cooperation Council (GCC) countries. Multiple sclerosis contributes to significant burden on patients and caregivers. The pharmacological treatment in MS involves treating acute exacerbations and preventing relapses and disability progression using disease-modifying therapies. Clinical evidence suggests that teriflunomide is one of the therapeutic choices for patients with relapsing-remitting MS (RRMS). However, genetic and cultural differences across different regions may contribute to variations in drug use. Therefore, it is necessary to consider real-world evidence for teriflunomide usage in GCC countries. Methods: An expert group for MS gathered from GCC countries in December 2020. The consensus highlighting role of teriflunomide in MS management has been developed using clinical experiences and evidence-based approach. Results: The expert-recommended patient profile for teriflunomide usage includes individuals aged 18 years and above, both men and women (on effective contraceptives) with clinically isolated syndrome or RRMS. The factors considered were cost-effectiveness of the drug, patient preference, adherence, monitoring, established safety profile, and coronavirus disease 2019 status. Conclusion: Expert recommendations based on their clinical experience will be more helpful to clinicians in clinical settings regarding the usage of teriflunomide and provide valuable insights applicable in day-to-day practice.

Pattern reversal visual evoked potentials (prVEPs) in autosomal recessive hereditary spastic paraplegia with thin corpus callosum (ARHSPTCC) patients with SPG 11 mutations in Saudi Arabia, cross section hospital base study.

OBJECTIVE: To retrospectively report prVEPs in SPG11 ARHSP-TCC. BACKGROUND: ARHSPTCC is characterized by a thin corpus callosum, progressive spastic paraparesis, cognitive decline,and axonal neuropathy by SPG11 mutations. Additionally, seizures, cerebellar ataxia, speech and swallowing problems, extrapyramidal signs, and skeletal deformities may occur. Neuroradiological findings include thinning of the anterior corpus callosum (TCC), periventricular white matter changes, and cortical atrophy. Electromyography and nerve conduction studies may reveal axonal neuropathy or anterior horn involvement. However, optic nerve involvement and prVEPs have not been well described. DESIGN/METHODS: Routine prVEPs were performed in 11 subjects with genetically confirmed (Athena Diagnostic USA) SPG11 ARHSPTCC. Independent stimulation of each eye with a full-field checkerboard pattern reverse stimulation technique was performed. Repetitive waveforms were averaged and the P-100 was recorded. RESULTS: Eleven subjects aged 20 to 37 years were studied, 5 were female. Nine were from consanguineous parents. Nine had a family history and 3 pairs were siblings. Nine had TCC, 8 had diffuse brain atrophy and 1 had cerebellum and brainstem atrophy. Additionally, 9 had bilaterally abnormal prVEPs. The mean P100 latency of the left eye was 129.45 ms±19.47, and a mean amplitude of 7 µV±2.33, while the right had a mean P100 of 127.72 ms±12.69, and mean amplitude of 6.74 µV±2.84. CONCLUSIONS: Abnormal prVEPs occurred in 81.82% of our subjects with significantly prolonged P100 bilateral responses. This indicates that the visual pathway is affected in patients with SPG11 ARHSPTCC. However, no specific mutation was predominant. prVEPs should be considered in the routine evaluation for spastic paraparesis.

Serum Based miRNA as a Diagnostic Biomarker for Multiple Sclerosis: a Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to identify deferentially expressed serum miRNAs in multiple sclerosis patients and to evaluate their diagnostic value in multiple sclerosis diagnosis. Studies were identified on PubMed, Google scholar and Saudi digital library up to 30 September 2019. Articles that examined miRNA expression level in MS patients compared to healthy control group were included in the review and the data were extracted by three independent author. The comprehensive Meta-Analysis version 3 software was used for meta-analysis and heterogeneity of studies was identified according to I2 value. Our literatures search identified 9 eligible articles concerning the serum miRNA as a diagnostic biomarker for multiple sclerosis in comparison to healthy control group. 19 serum miRNAs differentially expressed in MS patients were identified (8 downregulated, 11 upregulated and 1 with discordant result). In publications that provided information on specific miRNA diagnostic value, the pooled AUC was 72% (95% CI 0.65-0.78, p-value 0.00) for the overall multiple sclerosis patients and primary progressive MS (PPMS) (95% CI 0.66-0.78 p-value 0.00). A miRNA panel of four miRNAs showed high sensitivity (73%) and specificity (68%) in distinguishing multiple sclerosis from control groups. When using single miRNA (miR-145), the sensitivity increased to 79% and the specificity to 87%. The available data from the literature and this meta-analysis suggests the potential use of serum miRNA as biomarkers for early diagnosis of MS with high sensitivity and specificity in distinguishing multiple sclerosis subtypes from healthy controls.Abbreviation: MS: Multiple sclerosis; IDD: inflammatory demyelinating diseases; RRMS: relapsing-remitting Multiple sclerosis; PPMS: primary progressive Multiple sclerosis; SPMS: secondary progressive Multiple sclerosis; NMO: Neuromyelitis optica; miRNA: microRNA; ECmiRNA: extracellular microRNA; AUC: Area Under the Curve; ROC: Receiver Operator Characteristic.

Acute reversible rhabdomyolysis during direct-acting antiviral hepatitis C virus treatment: a case report.

INTRODUCTION: Treatment of hepatitis C infection has evolved dramatically since 2011. Previous conventional therapy with interferon and ribavirin used to have a low sustained virological response rate of less than 40%. In the new direct-acting antiviral therapy era, a sustained virological response can be achieved in more than 90% of cases. CASE PRESENTATION: We report a rare case of severe reversible acute rhabdomyolysis in a 31-year-old Saudi male patient with very long-chain acyl-coenzyme A dehydrogenase deficiency and chronic hepatitis C infection. The patient was clinically asymptomatic with no signs of decompensated liver disease. The patient received new direct-acting antiviral agents: sofosbuvir and daclatasvir. Fourteen days after initiation of direct-acting antiviral agents, the patient was found to have asymptomatic rhabdomyolysis. His creatine kinase peaked at 2572 IU/l, and he was treated conservatively; the direct-acting antiviral agents were discontinued and within 7 days, the patient's creatine kinase levels normalized. CONCLUSION: This case highlights possible direct-acting antiviral agent-induced rhabdomyolysis in a patient with very-long-chain acyl-CoA dehydrogenase deficiency, presumably through alteration of mitochondrial membrane potential. Further studies are required to assess the possible impact and associations.

Prevalence of Pediatric Onset Multiple Sclerosis in Saudi Arabia.

BACKGROUND: The prevalence of multiple sclerosis (MS) appears to be increasing worldwide. However, data on the pediatric onset of MS is lacking, particularly in developing countries. OBJECTIVE: This study is aimed at reporting the current burden of the pediatric onset of MS in the five regions of Saudi Arabia. METHODS: This study used relevant data from the National Saudi MS Registry that was operational between 2015 and 2018. The data on patients with pediatric onset MS from all the hospitals included in the registry was retrospectively analyzed using the age of diagnosis. Patients who were 1-18 years old when diagnosed were included in the analysis. RESULTS: The registry included 287 patients with pediatric onset MS, with a mean age of diagnosis at 15.7 (SD: 2.06). 74.2% of the participants were females. For the included hospitals, the estimated prevalence of pediatric MS was at 2.73/100,000 pediatric Saudi population. The prevalence of pediatric MS in the remaining nonparticipant hospitals was then projected taking into account both the size of pediatric population in the Kingdom per region and the number of facilities treating and managing MS in each of the corresponding regions. The overall projected prevalence was found to be 14.33/100,000 Saudi pediatric population. CONCLUSION: To the best of our knowledge, this study reported the latest epidemiological data of pediatric onset of MS in Saudi Arabia. The current prevalence of MS among the pediatric Saudi population was found to be 2.73/100,000, and the overall projected prevalence was estimated at 14.33/100,000. Our findings were similar to those in other pediatric MS cohorts. Further studies are needed to understand the long-term prognosis, response to treatment, and disease course.

Managing multiple sclerosis in the Covid19 era: a review of the literature and consensus report from a panel of experts in Saudi Arabia.

Disease-modifying therapies (DMT) for relapsing-remitting MS (RRMS) act on the immune system, suggesting a need for caution during the SARS-CoV2/Covid-19 pandemic. A group of experts in MS care from Saudi Arabia convened to consider the impact of Covid-19 on MS care in that country, and to develop consensus recommendations on the current application of DMT therapy. Covid-19 has led to disruption to the care of MS in Saudi Arabia as elsewhere. The Expert Panel considered a DMT's overall tolerability/safety profile to be the most important consideration on whether or not to prescribe at this time. Treatment can be started or continued with interferon beta, teriflunomide, dimethyl fumarate, or natalizumab, as these DMTs are not associated with increased risk of infection (there was no consensus on the initiation of other DMTs). A consensus also supported continuing treatment regimens with fingolimod (or siponimod) and cladribine tablets for a patient without active Covid-19. No DMT should be imitated in a patient with active Covid-19, and (only) interferon beta could be continued in the case of Covid-19 infection. Vaccination against Covid-19 is a therapeutic priority for people with MS. New treatment should be delayed for 2-4 weeks for vaccination. Where treatment is already ongoing, vaccination against Covid-19 should be administered immediately without disruption of treatment (first-line DMTs, natalizumab, fingolimod), when lymphocytes have recovered sufficiently (cladribine tablets, alemtuzumab) or 4 months after the last dose (ocrelizumab). These recommendations will need to be refined and updated as new clinical evidence in this area emerges.

A Prospective Multicenter Study for Assessing MusiQoL Validity among Arabic-Speaking MS Patients Treated with Subcutaneous Interferon ß-1a.

Few studies examine health-related quality of life (HRQoL) in Arabic-speaking multiple sclerosis (MS) patients. However, HRQoL tools such as the Short Form-36 QoL instrument (SF-36) and the Multiple Sclerosis International QoL (MusiQoL) questionnaire have been validated in other languages. The primary objective of this study was to prospectively assess HRQoL using the MusiQoL questionnaire among Arabic-speaking MS patients treated with subcutaneous interferon (sc IFN ß-1a) over 12 months, as part of a prospective, multinational, multicenter cohort study. Patients' clinical parameters and HRQoL were assessed at baseline, 6 months, and 12 months. Changes in MusiQoL total and subdomain scores were compared using a Friedman test. Correlation between MusiQoL total score and Expanded Disability Status Score (EDSS) was also evaluated. In total, 439 patients from four Arabic-speaking countries were included. The mean age was 32.44 (±0.34) years, 71.5% were female, and 63.1% had an education level of university or above. The mean MS duration was 4.13 (±0.12) years, mean age at first attack was 27.35 (±0.26) years, and mean baseline EDSS score was 2.05 (±0.04). MusiQoL total score significantly improved at 6 months; however, this diminished at 12 months (65.67 ± 0.8 at baseline vs. 67.21 ± 0.79 at 6 months and 65.75 ± 0.8 at 12 months; p = 0.0015). Several aspects of patients' HRQoL including activity of daily living, physical well-being, symptoms, and coping improved. Overall HRQoL measured using SF-36 remained generally unchanged over time (p = 0.215). There was a statistically significant inverse relationship between change in EDSS score over time and change in overall MusiQoL score over time. In summary, findings confirm the utility of using MusiQoL for assessing changes in HRQoL during treatment with sc IFN ß-1a in Arabic-speaking patients with MS.

Family Planning for People with Multiple Sclerosis in Saudi Arabia: an Expert Consensus.

More than half of all patients with multiple sclerosis (MS) in the Kingdom of Saudi Arabia (KSA) are women of childbearing age. Raising a family is an important life goal for women in our region of the world. However, fears and misconceptions about the clinical course of relapsing-remitting MS (RRMS) and the effects of disease-modifying drugs (DMDs) on the foetus have led many women to reduce their expectations of raising a family, sometimes even to the point of avoiding pregnancy altogether. The increase in the number of DMDs available to manage RRMS and recent studies on their effects in pregnancy have broadened management options for these women. Interferon beta now has an indication in Europe for use during pregnancy (according to clinical need) and can be used during breastfeeding. Glatiramer acetate is a further possible option for women with lower levels of RRMS disease activity who are, or about to become, pregnant; natalizumab may be used up to 30 weeks in patients with higher levels of disease activity. Where possible, physicians need to support and encourage women to pursue their dream of a fulfilling family life, supported where necessary by active interventions for RRMS that are increasingly evidence based.

Further delineation of MYO18B-related autosomal recessive Klippel-Feil syndrome with myopathy and facial dysmorphism.

Klippel-Feil syndrome 4 (KFS4; MIM# 616549) is an autosomal recessive disorder caused by biallelic pathogenic variants in MYO18B and comprises, in addition to Klippel-Feil anomaly (KFA), nemaline myopathy, facial dysmorphism, and short stature. We aim to outline the natural history of KFS4 and provide an updated description of its clinical, radiological, laboratory, and molecular findings. We comprehensively analyzed the medical records of 6 Saudi and 1 American patients (including 5 previously unpublished cases) with a molecularly confirmed diagnosis of KFS4. All patients had myopathy of varying severity that followed a slowly progressive or non-progressive course, affecting primarily the proximal musculature of the lower limb although hand involvement with distal arthrogryposis and abnormal interphalangeal creases was also observed. KFA and characteristic dysmorphic features, including ptosis and bulbous nose, were observed in all but two patients. The causal MYO18B variants were a founder NM_032608.5:c.6905C>A; p.(Ser2302*) variant in the Saudi patients (P1-P6) and a novel MYO18B homozygous variant (c.6660_6670del;p.[Arg2220Serfs*74]) in the American Caucasian patient (P7). We report the phenotypic and genetic findings in seven patients with KFS4. We describe the natural history of this disease, confirm myopathy as a universal feature and describe its pattern and progression, and note interesting differences between the phenotypes observed in patients with KFA and those without.

Amyotrophic lateral sclerosis care in Saudi Arabia: A survey of providers' perceptions.

OBJECTIVE: Provision of care for patients with amyotrophic lateral sclerosis (ALS) is complex and requires the contribution of multiple healthcare professionals. Several international ALS care measures were developed to ensure optimal care for ALS patients. We looked at the rate of inconsistency in providing standard ALS care measures in Saudi Arabia (SA). METHODS: A 5-point response survey was distributed to practicing neurologists in SA. They were asked to grade their perceived consistency of accessibility for 19 items of ALS care measures at their center. The list of ALS care measures items was derived from international ALS guidelines. RESULTS: The response rate from neurologists was 47.3% (62/131), and the responses of 39 neurologists who follow ALS cases were included. Most of the selected ALS care measure items, 63.1% (12/19), were perceived by 50% or more of the ALS care providers to be not consistently accessible to their patients. The perception of ALS care providers of the inconsistent accessibility for ALS patients to ALS care measures was high for communication devices (92.3%), supportive equipment such as motorized wheelchairs (76.9%), end-of-life discussion (74.4%), and respiratory monitoring (66.7%). CONCLUSION: Our data show that ALS patients in SA do not have consistent access to the recommended ALS care measures.

Cladribine Tablets and Relapsing-Remitting Multiple Sclerosis: A Pragmatic, Narrative Review of What Physicians Need to Know.

Immune reconstitution therapy (IRT) is an emerging management concept for multiple sclerosis, whereby a short course of treatment provides long-lasting suppression of disease activity. "Cladribine tablets 10 mg" refers to a total cumulative dose of cladribine given over 2 years (henceforth referred to as cladribine tablets 3.5 mg/kg); it is a relatively new treatment option that is hypothesised to act as an IRT acting preferentially on the adaptive immune system. A randomised, 2-year, placebo-controlled trial (CLARITY) showed that treatment with cladribine tablets reduced indices of disease activity (relapses, lesions on magnetic resonance images, disability progression) and that this effect outlasted the pharmacologic effect of the treatment on the immune system (mainly a reduction in circulating B and T cells, with little effect on components of the innate immune system such as monocytes). CLARITY Extension, a 2-year extension to this trial, demonstrated durable efficacy, also in patients who received the standard 2-year course of cladribine tablets 3.5 mg/kg and were re-randomised to placebo for a further 2 years. Relative risk reductions for relapse rate with cladribine tablets 3.5 mg/kg were similar for patients with or without prior high disease activity. Reductions in disability progression with cladribine tablets 3.5 mg/kg were higher in patients with prior high relapse rates with or without prior treatment non-response. In this review, we describe the therapeutic profile of cladribine tablets 3.5 mg/kg and provide practical information on initiating this treatment option in the most appropriate patients.

Current management of Duchenne muscular dystrophy in the Middle East: expert report.

Aim: Duchenne muscular dystrophy (DMD) is a severe and rare X-linked neuromuscular childhood disorder that results in functional decline, loss of ambulation and early death due to cardiac or respiratory failure. The objective of this paper is to address different aspects of the current management of DMD in the Middle East, north Africa (MENA) region, and to gather experts' recommendations on how to optimally diagnose and treat patients suffering from this disease. Methods: A group of experts (neuromuscular medicine, neuropediatricians and geneticists) convened to discuss the diagnosis and management of DMD in the MENA region. A list of practical statements was prepared by the chair of the meeting to guide the discussions around critical aspects relating to the current and future management of DMD. Results & conclusion: Ideally, DMD management should be a multidisciplinary approach. Nevertheless, few tertiary care hospitals in the region are currently able to provide the full spectrum of medical expertise and services needed by DMD patients. Clinical practice in the region remains heterogeneous. Specific guidelines for diagnosis and treatment are needed in the MENA region to improve outcomes. Disease awareness among the general public and the medical community is lacking. Now that mutation-specific therapies are being developed and more widely studied, general education programs regarding early signs and symptoms, a standardized referral and diagnosis pathway, patient registries and support groups will significantly improve the management of the disease.